Ferrier rearrangement
# Ferrier rearrangement

The Ferrier rearrangement is an organic reaction that involves a nucleophilic substitution reaction combined with an allylic shift in a glycal (a 2,3-unsaturated glycoside). It was discovered by the carbohydrate chemist Robert J. Ferrier.

## Mechanism

In the first step, a delocalized allyloxocarbenium ion (2) is formed, typically with the aid of a Lewis acid like indium(III) chloride or boron trifluoride. This ion reacts in situ with an alcohol, yielding a mixture of the α (3) and β (4) anomers of the 2-glycoside, with the double bond shifted to position 3,4.

## Examples

| Lewis acid | Alcohol | Conditions | Results |
| - | - | - | - |
| $InCl_3$ | methanol | in dichloromethane | α:β = 7:1 |
| dioxane | water | heating | 75% yield |
| $SnCl_4$ | methanol | in dichloromethane, –78 °C, 10 min | 83% yield, α:β = 86:14 |
| $BF_3·O(C_2H_5)_2$ | isopropanol | in dichloromethane, RT, 24 hr | 95% yield |
| $ZnCl_2$ | ethanol | in toluene, RT, 30–60 min | 65–95% yield, α:β = 89:11 |
| $BF_3·O(C_2H_5)_2$ | benzyl alcohol | in dichloromethane, –20 °C to RT, 1 hr | 98% yield |

## Modifications

### Forming of C-glycosides

By replacing the alcohol with a silane, C-glycosides can be formed. With triethylsilane (R'=H), the reaction yields a 2,3-unsaturated deoxy sugar.

### Nitrogen analogue

An analogous reaction with nitrogen as the heteroatom was described in 1984 for the synthesis of the antibiotic substance streptazolin.

